Goodson U.S. Pat. No. 4,764,377 describes an intra-pocket drug delivery device for the treatment of periodontal disease. The therapeutic agent delivery device may be packed into a periodontal pocket formed in the gum tissue against the root of the tooth where a chronic infection such as pyorrhea exists. The packing material of the Goodson patent is a string-like polymeric material which carries a concentration of an antibiotic such as teiracycline for controlled release of the tetracycline over a period of time into the periodontal cavity. By this technique, a continuous delivery of an antibiotic may be provided for the elimination of chronic infection.
Additionally, the Goodson patent teaches a diffusion limiting surface about a stringlike therapeutic agent delivery device, apparently to control the rate of diffusion of tetracycline or other antibiotic from the plastic material in which it resides.
As one disadvantage of the above system, the antibiotic which diffuses out of the polymeric carrier will rapidly disperse out of the periodontal pocket by diffusion through the tissue. Also, the rate of antibiotic diffusion is of course constant and predictable whether or not there is a substantial concentration of bacteria present or not.
It would be desirable to provide a controlled release vehicle for antibiotics in a packing material for the treatment of infections in which the diffusion rate of antibiotic can be effectively slowed, but that the concentration of free antibiotic present can increase in a manner which is dependent upon the concentration of bacteria present. Thus, in a chronic situation when bacterial infections may appear and disappear, such a packing material would tend to retain its supply of antibiotic when the concentration of harmful bacteria present was very low, but the release of free antibiotic would increase as the concentration of bacteria increased. This would form a long-lived, self-regulating system to keep the area containing the packing material substantially free of infection.
Such a system is provided in accordance with this invention, in which a minimum, desired concentration of free antibiotic is released under circumstances where the bacteria concentration is low, but in the event of significant infection the release of antibiotic from the packing material of this invention can increase in response to the infectious conditions. Thus, the packing material of this invention can have a longer useful life when placed in an infection-prone tissue pocket or the like, since under conditions of low bacterial concentration a low concentration of free antibiotic is released. However, but when the need arises, higher amounts of antibiotic are released in response to higher concentrations of bacteria present.
Additionally, in this invention the antibiotic may be stored in a prodrug form which, if it diffuses from the packing material, is less permeable through tissue, so that it tends to be retained in the body cavity into which it is released.